Retinoids are a class of lipophilic isoprenoid molecules chemically related vitamin A. The retinoids possess a β-ionone ring and a polyunsaturated side chain with an alcohol (for example, retinol), an aldehyde (for example, retinal), a carboxylic acid (for example, retinoic acid) group or an ester (for example, retinyl acetate) functional group. It is known that the retinoids have essential roles in human health such as eye protection, bone development and regeneration, and providing antioxidative effects, and skin anti-aging, and decrease a risk of certain cancers.
In recent years, the retinoids have received great attention as effective cosmetics and medicine sources for anti-wrinkle and skin disease treatment. The worldwide retinoid market size is estimated at about 16 billion dollars. Chemically synthesized retinoids are representative commercial sources. Retinol is produced through acidification or hydrolysis of chemically synthesized retinal due to reduction of pentadiene derivatives. However, such chemical processes have disadvantages such as a complex purification operation and undesired by-product formation. Animals produce retinoids from carotenoids obtained from fruits and vegetables, but plants are unable to synthesize retinoids. A complete pathway in retinoid synthesis is possible only in microorganisms having bacteriorhodopsin or proteorhodopsin that includes retinal as a prosthetic group. However, since microorganisms produce retinal-binding protein forms, it is inappropriate for mass production of free retinoids. Limited attempts for biological production using enzymes have been tried so far, but the results were unsuccessful. Therefore, it is necessary to develop a biotechnological method for producing retinoids using metabolically transformed microorganisms.
Retinoids are chemically very unstable and easily oxidized and isomerized by heat, oxygen and light due to their reactive conjugated double bonds. Also, retinoids are easily biodegraded by retinoic acid. Therefore, a method of producing retinoids more efficiently is necessary.
In Korean Laid-open Patent Application No. 2008-42387, a method of mass-producing an isoprenoid, E. coli transformed with carotenoid biosynthesis genes and astaxanthin using the same is disclosed.
[Patent Literature] Korean Laid-open Patent Application No. 2008-42387